DESCRIPTION: (Applicant's Abstract) The problem of endemic hepatitis C virus (HCV) infection in injection drug users (IDUs) is only beginning to be recognized, although HCV infection rates in IDUs consistently exceed the incidence of HIV or HBV. Research to date has not provided the basis for development of urgently- needed HCV prevention programs. With the long-term goal of contributing to knowledge that will lead to interventions to prevent HCV infection in drug injectors, the specific aims of this study are the following: Aim 1. Describe the epidemiology of HCV infection in IDUs. We will measure HCV incidence in a cohort of 400 HCV-seronegative IDUs over a three year period, in relation to demographic characteristics, injection and sexual risk behaviors, and participation in harm reduction programs such as needle exchange and drug treatment. Aim 2. Study the molecular epidemiology of HCV transmission 1) within IDU social networks and 2) between IDUs and other patient groups in the community. Using a case-control design, we will study the social networks of 40-50 cohort members (Aim 1) who seroconvert to HCV-positive (index subjects), and examine genetically related infections in network members in relation to risk behavior with the index subject. Risk network members will include those who used drugs with or had sexual contact with the index subject during the time period when the index acquired HCV infection. Molecular virology methods will be used to classify risk network members as related vs. unrelated strains. We will also study characteristics of social networks associated with diffusion of HCV in the network, as indicated by overall HCV-prevalence in the network, the presence of multiple genotypes in the network, and the presence of IDUs in the network who are infected with multiple strains. Additionally, we will compare the genetic distance between HCV strains in IDU subjects to that in other patient groups in the community, to assess the degree of transmission between IDUs and other patients. The significance of this study will be its contribution to our understanding of HCV epidemiology and risk factors that may be used to develop appropriate prevention strategies. The study will also increase awareness of the magnitude of the problem of HCV by measuring incident infections and investigating whether IDUs represent an important source of HCV transmission to other segments of the population.